How to Treat a Signal? Current Basis for RET-Genotype-Oriented Choice of Kinase Inhibitors for the Treatment of Medullary Thyroid Cancer

The significance of RET in thyroid cancer comes from solid evidence that, when inherited, an RET activating mutation primes C-cells to transform into medullary carcinomas. Moreover, environmental exposure to radiation also induces rearranged transforming RET “isoforms” that are found in papillary th...

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Main Authors:	Prazeres, Hugo, Torres, Joana, Rodrigues, Fernando, Couto, Joana P., Vinagre, João, Sobrinho-Simões, Manuel, Soares, Paula
Format:	Online
Language:	English
Published:	SAGE-Hindawi Access to Research 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134398/

id	pubmed-3134398
recordtype	oai_dc
spelling	pubmed-31343982011-07-15 How to Treat a Signal? Current Basis for RET-Genotype-Oriented Choice of Kinase Inhibitors for the Treatment of Medullary Thyroid Cancer Prazeres, Hugo Torres, Joana Rodrigues, Fernando Couto, Joana P. Vinagre, João Sobrinho-Simões, Manuel Soares, Paula Review Article The significance of RET in thyroid cancer comes from solid evidence that, when inherited, an RET activating mutation primes C-cells to transform into medullary carcinomas. Moreover, environmental exposure to radiation also induces rearranged transforming RET “isoforms” that are found in papillary thyroid cancer. The RET gene codes for a tyrosine kinase receptor that targets a diverse set of intracellular signaling pathways. The nature of RET point mutations predicts differences in the mechanisms by which the receptor becomes activated and correlates with different forms of clinical presentation, age of onset, and biological aggressiveness. A number of RET-targeting Tyrosine Kinase Inhibitors (TKIs) are currently undergoing clinical trials to evaluate their effectiveness in the treatment of thyroid cancer, and it is conceivable that the RET genotype may also influence response to these compounds. The question that now emerges is whether, in the future, the rational for treatment of refractory thyroid cancer will be based on the management of an abnormal RET signal. In this paper we address the RET-targeting TKIs and review studies about the signaling properties of distinct RET mutants as a means to predict response and design combinatorial therapies for the soon to be available TKIs. SAGE-Hindawi Access to Research 2011-06-23 /pmc/articles/PMC3134398/ /pubmed/21765992 http://dx.doi.org/10.4061/2011/678357 Text en Copyright © 2011 Hugo Prazeres et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Prazeres, Hugo Torres, Joana Rodrigues, Fernando Couto, Joana P. Vinagre, João Sobrinho-Simões, Manuel Soares, Paula
spellingShingle	Prazeres, Hugo Torres, Joana Rodrigues, Fernando Couto, Joana P. Vinagre, João Sobrinho-Simões, Manuel Soares, Paula How to Treat a Signal? Current Basis for RET-Genotype-Oriented Choice of Kinase Inhibitors for the Treatment of Medullary Thyroid Cancer
author_facet	Prazeres, Hugo Torres, Joana Rodrigues, Fernando Couto, Joana P. Vinagre, João Sobrinho-Simões, Manuel Soares, Paula
author_sort	Prazeres, Hugo
title	How to Treat a Signal? Current Basis for RET-Genotype-Oriented Choice of Kinase Inhibitors for the Treatment of Medullary Thyroid Cancer
title_short	How to Treat a Signal? Current Basis for RET-Genotype-Oriented Choice of Kinase Inhibitors for the Treatment of Medullary Thyroid Cancer
title_full	How to Treat a Signal? Current Basis for RET-Genotype-Oriented Choice of Kinase Inhibitors for the Treatment of Medullary Thyroid Cancer
title_fullStr	How to Treat a Signal? Current Basis for RET-Genotype-Oriented Choice of Kinase Inhibitors for the Treatment of Medullary Thyroid Cancer
title_full_unstemmed	How to Treat a Signal? Current Basis for RET-Genotype-Oriented Choice of Kinase Inhibitors for the Treatment of Medullary Thyroid Cancer
title_sort	how to treat a signal? current basis for ret-genotype-oriented choice of kinase inhibitors for the treatment of medullary thyroid cancer
description	The significance of RET in thyroid cancer comes from solid evidence that, when inherited, an RET activating mutation primes C-cells to transform into medullary carcinomas. Moreover, environmental exposure to radiation also induces rearranged transforming RET “isoforms” that are found in papillary thyroid cancer. The RET gene codes for a tyrosine kinase receptor that targets a diverse set of intracellular signaling pathways. The nature of RET point mutations predicts differences in the mechanisms by which the receptor becomes activated and correlates with different forms of clinical presentation, age of onset, and biological aggressiveness. A number of RET-targeting Tyrosine Kinase Inhibitors (TKIs) are currently undergoing clinical trials to evaluate their effectiveness in the treatment of thyroid cancer, and it is conceivable that the RET genotype may also influence response to these compounds. The question that now emerges is whether, in the future, the rational for treatment of refractory thyroid cancer will be based on the management of an abnormal RET signal. In this paper we address the RET-targeting TKIs and review studies about the signaling properties of distinct RET mutants as a means to predict response and design combinatorial therapies for the soon to be available TKIs.
publisher	SAGE-Hindawi Access to Research
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134398/
_version_	1611464959065063424

How to Treat a Signal? Current Basis for RET-Genotype-Oriented Choice of Kinase Inhibitors for the Treatment of Medullary Thyroid Cancer

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